Apparatus and method for irradiating a medium

ABSTRACT

A method for irradiating a medium with a wave which is designed to focus on a particular portion in the medium, the method includes: irradiating the medium with an electromagnetic wave which is scattered in the medium, and is not designed to focus on the particular portion in the medium; detecting a first signal caused by irradiating the medium with the electromagnetic waver; irradiating the medium with a reconstructed wave which is designed to focus on the particular portion in the medium; detecting a second signal caused by irradiating the medium with the reconstructed wave; and monitoring, based on the first and second signals, that the particular portion is irradiated by the reconstructed wave.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an apparatus and a method forirradiating a medium.

2. Description of the Related Art

Light scattering is one of the essential matters that can obstruct andeven prevent viewing inside of, or through, a medium where scatteringprocesses are dominant. This is because the scattered light does notpropagate in a straight line through the medium, with the random pathsof the scattered light causing the loss of directionality of the lightas well as information associated therewith. Thus, it can be difficultto extract detailed internal information about a medium in which suchscattering occurs via the detection of the scattered or diffused visiblelight. For example, in medical applications that deal with biologicaltissues, the scattering that occurs in passing light through the tissuesmay make it difficult to obtain internal information via detection ofthe scattered light.

In addition, there is also increasing demand to be able to concentratelight energy at a target position in a scattering medium, such as forexample to allow for treatment of abnormal tissue in photodynamictherapy, as well as to achieve unique and promising functions that wereheretofore unobtainable in intentionally disordered random materials.

The ability to focus light at a point inside of or through a scatteringmedium has not been achieved until fairly recently. However, in recentyears, a technique has been proposed which optimizes a wavefront ofincident light to suppress the scattering effect.

In U.S. Patent Application Publication No. 2009/0009834, an opticalphase conjugation technique is disclosed that can be used to record awavefront of scattered light transmitted through a scattering medium bya holographic recording material, and to generate a phase conjugationwave, which has a phase substantially opposite to the phase of therecorded wavefront. The phase conjugation wave is generated such that itis configured to enter the scattering medium and to be viewable throughthe scattering medium.

Since elastic optical scattering is a deterministic and time-reversibleprocess, the optical phase conjugation can retrace its trajectory backthrough the scattering medium to its original incident point. The methodas disclosed in U.S. Patent Application Publication No. 2009/0009834utilizes this ability, which can be effective in suppressing thescattering effect and enhancing the spatial resolution of the imagesobtained of the scattering medium.

However, U.S. Patent Application Publication No. 2009/0009834 disclosesthat the optical phase conjugation method described therein is onlycapable of focusing light at a region just behind the scattering medium,where the incident light originally impinges. Therefore, as describedtherein, the method is not being capable of focusing light arbitrarilyat any specific point inside the scattering medium.

SUMMARY OF THE INVENTION

Embodiments of the present invention provide an apparatus and a methodfor irradiating a medium.

According to an aspect of the present invention, a method forirradiating a medium with a wave which is designed to focus on aparticular portion in the medium is provided, the method includesirradiating the medium with an electromagnetic wave which is scatteredin the medium, and is not designed to focus on the particular portion inthe medium; detecting a first signal caused by irradiating the mediumwith the electromagnetic wave; irradiating the medium with areconstructed wave which is designed to focus on the particular portionin the medium; detecting a second signal caused by the irradiating themedium with the reconstructed wave; and monitoring, based on the firstand second signals, that the particular portion is irradiated by thereconstructed wave.

According to another aspect of the present invention, an apparatus isprovided for irradiating a medium with a wave which is designed to focuson a particular portion in the medium. The apparatus includes: a firstirradiating unit configured to irradiate the medium with anelectromagnetic wave which is scattered in the medium, and is notdesigned to focus on the particular portion in the medium; a secondirradiating unit configured to irradiate the medium with a reconstructedwave which is designed to focus on the particular portion in the medium;a detecting unit configured to detect a first signal caused by the firstirradiating unit and a second signal caused by the second irradiatingunit; and a monitoring unit configured to monitor, based on the firstand second signals, that the particular portion is irradiated by thereconstructed wave.

According to another aspect of the present invention, an apparatus isprovided that includes: a light source configured to irradiate a mediumwith an electromagnetic wave, and to be used for a reference wave; amodulator configured to modulate a frequency of the electromagnetic waveat a particular portion in the medium; a first detector configured toobtain information related to an interference pattern formed byinterference of the modulated electromagnetic wave with the referencewave; a generator configured to generate an electromagnetic wave lightbeam which is scattered in the medium, and is not designed to focus onthe particular portion in the medium, and configured to generate areconstructed wave which is designed, based on the obtained information,so as to focus on the particular portion in the medium; and a seconddetector configured to detect a first signal from the medium, caused bythe electromagnetic wave, and configured to detect a second signal fromthe medium, caused by the reconstructed wave.

According to another aspect of the present invention, an apparatus isprovided that includes: a light source configured to irradiate a mediumwith an electromagnetic wave, a frequency of which is modulated at aparticular portion in the medium, and configured to be used for areference wave; a holographic material configured to acquire informationrelated to an interference pattern formed by interference of themodulated electromagnetic wave with the reference wave, and forgenerating a reconstructed wave which is designed, based on the acquiredinformation, so as to focus on the particular portion in the medium; anda detector configured to detect a first signal from the medium when awave, which is scattered in the medium and is not designed to focus onthe particular portion in the medium, is irradiated to the medium, andconfigured to detect a second signal from the medium, caused by thereconstructed wave.

According to another aspect of the present invention, an apparatus isprovided that includes: a light source configured to irradiate a mediumwith an electromagnetic wave, a frequency of which is modulated at aparticular portion in the medium, and configured to be used for areference wave; a holographic material holding unit configured to hold aholographic material for acquiring information related to aninterference pattern formed by interference of the modulatedelectromagnetic wave with the reference wave, and for generating areconstructed wave which is designed, based on the acquired information,so as to focus on the particular portion in the medium; and a detectorconfigured to detect a first signal from the medium when a wave, whichis scattered in the medium and is not designed to focus on theparticular portion in the medium, is irradiated to the medium, andconfigured to detect a second signal from the medium, caused by thereconstructed wave.

Further features of the present invention will become apparent from thefollowing description of exemplary embodiments with reference to theattached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates multiple scattered light in a scattering medium.

FIG. 1B illustrates “reemission” of frequency-shifted light in ascattering medium.

FIG. 1C illustrates light focusing in a scattering medium.

FIG. 2A illustrates an arrangement of a first step (recording process).

FIG. 2B illustrates an arrangement of a second step (reproducing processfor irradiation).

FIG. 3A illustrates an arrangement of a first step in an exemplaryembodiment.

FIG. 3B illustrates an arrangement of a second step in the exemplaryembodiment.

FIG. 4 illustrates an arrangement of another exemplary embodiment.

FIG. 5 illustrates an exemplary operation flow.

FIG. 6 illustrates an arrangement of another exemplary embodiment.

FIG. 7 illustrates an arrangement of a fifth embodiment.

FIG. 8 illustrates an exemplary operation flow.

DESCRIPTION OF THE EMBODIMENTS

Embodiments according to the present invention will be described belowwith reference to the attached drawings.

FIG. 1A illustrates multiple light scattering and a position 102 in ascattering medium 101. At the position 102, a frequency of an incidentlight beam 100 can be modulated. Once the incident light beam 100 entersthe scattering medium 101 including scattering particles 199, the light100 undergoes multiple scattering throughout the propagation in themedium 101 and eventually exits from the surface of the medium 101 asscattered light 103. At this time, a portion of the incident light 100can reach the position 102 and can be modulated in frequency at theposition 102. For example, an ultrasonic wave can be employed tomodulate the frequency of the incident light 100 at the position.Alternatively, a means which can modulate a frequency of the incidentlight at a local position in the medium may be available instead of theultrasonic wave.

In a technique called acousto-optic imaging or ultrasound modulatedtomography, when a scattering medium 101 is irradiated by an ultrasonicwave, the refractive index of the medium is modulated and in addition,the displacement of the scatterers in the scattering medium 101 isinduced with the frequency of the applied ultrasonic wave. Once theportion of the incident light 100 reaches an ultrasound irradiatedvolume at the position in the medium 101, the optical phase of the lightcan be modulated by the frequency of the ultrasonic wave, and thatcauses frequency-shift of the light.

FIG. 1B illustrates the generation and propagation of interacted(frequency-shifted) light 104 in the medium 101. The frequency of theinteracted light 104 is shifted (modulated) by the frequency of theultrasonic wave. Therefore, the frequency of the light 104 is differentfrom the incident light 100 and the scattered light 103 that is notmodulated by the ultrasonic wave. This frequency-shifted light 104originating from the ultrasound irradiated volume at the position 102keeps propagating while undergoing multiple scattering and exits fromthe medium 101.

In other words, the ultrasound irradiated volume at the position 102might act as if there is another light source inside the scatteringmedium 101 that generates light whose frequency is different from theoriginal one. This frequency-shifted light 104 clearly originates fromthe ultrasound irradiated volume at the position 102.

Once the wavefront corresponding mainly to this frequency-shifted light104 is recorded and is played back with its phase conjugation 105, thisphase conjugation can retrace its trajectory and reach or travel towardthe position 102 shown in FIG. 1C. To realize a phase conjugation (i.e.,a reconstructed wave, a phase conjugation wave), holography can beemployed. In holography, an interference pattern generated byinterference between the modulated light and a reference wave can berecorded in a holographic material, and also the interference patterncan be detected by a photodetector, such as a CCD sensor and a CMOSsensor. A technique to detect the interference pattern by thephotodetector is referred to as digital holography. The phase conjugatewave can be generated based on the obtained information related to theinterference pattern. For example, when the interference pattern isrecorded in the holographic material, the conjugate wave can begenerated by a pump light, as is mentioned in a latter part herein. Theholographic material, which might be a several mm by a several mm by aseveral mm cube, can be held by a holding unit (not shown).

On the other hand, when the information is obtained by the array sensor,the conjugate wave can be generated by using a generator such as aspatial light modulator (SLM), as described in a fourth embodimentherein.

A method of focusing irradiation in a scattering medium may generallyinvolve two steps. A first step is a recording step, and a second stepis a reproducing (reconstructing) step.

FIG. 2A shows an illustrative diagram of an arrangement for the firststep. A coherent light source 200 emits an initial light beam. Theinitial light can be split into an incident light beam 211 and areference light beam 212 by a beam splitter 201. Typically thewavelength emitted by the light source 200 can range from visible light(visible ray) to near-infrared light (near infrared ray). For example,an electromagnetic wave source that emits a wavelength from about 380 nmto about 2500 nm, such as from 400 nm to 1500 nm, may be used as thelight source 200.

External modulators such as acousto-optic modulators (AOM) 202 and 204can be driven independently by clocks of frequencies which are adjustedsuch that the frequency difference between them is approximately equalto the frequency applied to an ultrasound system 207. For example, ifthe frequency of the AOM 202 is f₁ (=70 MHz) and the frequency ofultrasound is f_(a) (=2 MHz), then the frequency f₂ of the AOM 204 isf₁+f_(a) (=72 MHz). The incident light beam 211 and reference light beam212 pass through the AOM 202 and AOM 204, respectively.

Another way to adjust the modulation frequency of those AOMs, is thatAOM 202 may be placed on the reference light beam 212 path instead of onthe incident light beam 211 path. Therefore, the reference light beam212 can pass through the two AOMs while incident light beam 211 does notpass through the AOM. The frequency of the first AOM can be set at, forexample, f₁=−70 MHz and the second one can be set at f₂=+72 MHz so thatf₁+f₂=2 MHz, which is equivalent to the ultrasound frequency f_(a) (=2MHz). Alternatively, the two AOMs can be placed on the incident lightbeam 211 path instead of the reference light beam 212 path with the samefrequency setting. When one AOM can offer a frequency which correspondsto the frequency of the ultrasound, there may be no need to use twoAOMs.

The ultrasound device 207 transmits an ultrasonic wave to create a focusvolume 208 whose size and position may be determined a priori. It may bepossible to radiate pulsed ultrasound to achieve a small longitudinalfocus volume. The pulse width of the ultrasound can be set depending onthe size of the focus volume 208 and the speed of the ultrasonic wave inthe scattering medium 209. Furthermore, stroboscopic irradiation by thelight source 200 can be used, where the timing of the irradiation fromthe light source 200 may be synchronized to irradiate the medium 209only during the time period when the ultrasound pulse locates theposition to be focused. To set the volume 208 at a position in themedium 209, a focused ultrasound may be employed.

A movable mirror 203 can be controlled and adjusted so that the incidentlight 211 enters the scattering medium 209. A first irradiating unit maycomprise a system including the light source 200 to irradiate the medium209, and optionally a controller to control the output of the lightsource 200. In the scattering medium 209, the incident light beam 211 ismultiply scattered, and some portion of the light can reach theultrasound focus volume 208 throughout the multiple scattering processand interact with ultrasound at a position of the volume 208.

The ultrasound focus volume 208 can re-emit the light asfrequency-shifted light as a consequence of the interaction between thelight and the ultrasound. At least a portion of the frequency-shiftedlight, as well as non-frequency-shifted light, reflects back and exitsfrom the surface of the medium 209 where the incident light 211 entered.A signal light beam which exits from the surface of the medium 209 isshown as a scattered wavefront 210. The scattered wavefront 210 can alsoexit from a position different from a point where the incident lightbeam 211 entered. This wavefront 210 impinges onto a holographicmaterial 206.

The reference light beam 212, which is adjusted to have the samefrequency as that of frequency-shifted light by AOM 204, can bereflected by the mirror 205 to illuminate the holographic material 206.A second irradiating unit may comprise a system to irradiate theholographic material 206, such as the mirror 205.

The interference between the signal light beam, which includes bothinteracted and non-interacted light, and the reference light beam 212,generates an interferogram inside the holographic material 206. Thisinterferogram may mainly consist of two components. One component is theinterference between the non-frequency-shifted light and the referencelight 212. The other component is the interference between thefrequency-shifted light and the reference light beam 212.

The former interference component, formed by the different lightfrequencies, moves as the speed of the beat frequency that is the sameas that applied to the ultrasound device 207. Typically this speed is sofast that the interference fringe is averaged out, and cannot beinscribed inside the holographic material 206. The latter interferencecomponent, formed by the same frequency, can create the staticinterference pattern inside the holographic material 206.

A bandpass filter may also be used to reject the non-frequency-shiftedlight and efficiently collect frequency-shifted light to form thehologram. For example, a Fabry-Perot interferometer, or acryogenically-cooled spectral hole burning crystal, may be suitable. Anarray sensor, such as a CCD sensor or a CMOS sensor, can also be used toobtain information related to the interference pattern, instead of theholographic material 206.

Consequently, the frequency-shifted light, which originates from thelocal ultrasound focus volume 208, can provide a main contribution increating the static hologram in the holographic material 206. In otherwords, information related to the interference between the referencelight beam and the frequency-shifted light can be recorded in theholographic material 206.

Since a phase conjugation of light can retrace its trajectory, the phaseconjugation of this inscribed wavefront can propagate back to theultrasound focus volume 208. This means that an incident light which isthe phase conjugation of the frequency-shifted light can focus back onthe local volume 208 in the scattering medium 209.

FIG. 2B shows an illustrative diagram of an arrangement for the secondstep, which is a reproducing step to irradiate the volume 208.

The light emitted by the light source 200 eventually illuminates theholographic material 206 as a pump light beam 213 in a directionsubstantially opposite to that of the reference light beam 212, as shownin FIG. 2B. Alternatively, another light source for the pump light canalso be employed instead of the light source 200, as described in athird embodiment. The first irradiating unit, after the information isrecorded on the holographic material, may thus be configured toirradiate the holographic material without passing through the medium209. The pump light beam 213 may be a continuous wave or a pulse wave.The frequency of the pump light beam 213 can be the same as thefrequency of the incident light 211. The reference light beam 212 cancontinue or suspend illuminating the holographic material 206 while thepump light beam 213 is illuminating the holographic material 206.

This pump light 213 generates a phase conjugation wave 210′ of therecorded wavefront inside the holographic material 206. The phaseconjugation wave 210′ propagates toward the scattering medium 209 andenters the medium 209. This phase conjugation wave 210′ can retrace itsoriginal trajectory experienced at the recording step in the scatteringmedium 209, and go back to the ultrasound focus volume 208. As a result,this local volume 208 can be focused by the phase conjugation light210′. In other words, the holographic material can generate areconstructed wave which irradiates the medium at the position in themedium, and the reconstructed wave can comprise the phase conjugate wavewhich travels to the position of the volume 208 in the medium 209. Acontroller, which controls an intensity of the reconstructed wave sothat the intensity of the reconstructed wave is different from that ofthe electromagnetic wave 211 used to obtain the modulatedelectromagnetic wave 210, may be additionally employed. The controllercan adjust the intensity of the light, for example, so that thereconstructed wave becomes weaker or stronger than the intensity of theelectromagnetic wave 211 used to obtain the modulated electromagneticwave 210 by using the controller. To detect a signal from the medium, aphotodetector and/or an ultrasound detector may be used. The signal fromthe medium can be an acousto-optic signal for an AOT image, and/or aphotoacoustic signal for a PAT image, and/or a diffuse optical signalfor a DOT image. The detector can be an image forming unit to form atomographic image using the signal output from the medium 209 inresponse to an irradiation thereof by the reconstructed wave.

The properties of the ultrasound focus volume 208 (e.g., volume size,shape, position) are controllable by operating the ultrasound device 207and its control unit (not shown). This feature may be quite important ina practical case. Therefore it may be possible to generate the phaseconjugation wave which is capable of retracing to a specific localvolume which is controllable inside the scattering medium. In short, thephase conjugate wave can be selectively delivered to a specific portionin the medium. The phase conjugate wave can be focused at the specificportions in the medium, compared to a region other than the specificportion. By applying this embodiment as either an irradiating apparatusor method in imaging which deals with multiple scattered light, thesignal-to-noise ratio (SNR) of the output image may be enhanced. Inaddition, this embodiment may improve the measurement depth of thatimaging method by focusing light inside the scattering medium. Theirradiating method can be applicable to various kinds of imaging methodsand other apparatuses that involve concentrating light in the scatteringmedium. The energy of the pump light beam 213 may also optionally beadjusted to be lower than the energy of light used to create a hologram.

Here, the scattering medium can be, for example, a biological tissue orany other turbid medium or disordered material.

The holographic material 206 can be a conventional emulsion, orphotorefractive crystal such as Lithium Niobate, Gallium Arsenide, BSO(Bismuth silicon oxide) or photorefractive polymer, for example,described in U.S. Pat. No. 6,653,421. Furthermore, a digital holographytechnique shown later may be applicable. The following are herebyincorporated by reference in their entireties as though fully andcompletely set forth herein: U.S. Pat. No. 6,653,421 to Yamamoto, issuedNov. 25, 2003, and U.S. Patent Application Publication No. 2009/0009834,published Jan. 8, 2009.

The holographic material can generate a phase conjugation wave, andinstead of using the holographic material such as emulsion orphotorefractive material, a combined system of an optical detector (suchas, a CCD or a CMOS sensor) and a spatial light modulator based ondigital holographic technique can be used. The spatial light modulatorcan generate a reconstructed wave.

The intensity of the frequency-shifted light might be large enough tocreate the hologram for generating the phase conjugation wave. Thisintensity depends on the position of the medium and the size of theultrasound focus volume 208 in the scattering medium 209. One of thepossible ways to set up the ultrasound focus point 208 in order to focuslight deep inside the scattering medium 209 may be to begin with thatultrasound focus point at a relatively shallower region where thefrequency-shifted light is relatively easily detected to form thehologram.

As a next step, the ultrasound focus point 208 may be set at a pointthat is a little bit deeper in the medium where the frequency-shiftedlight still can be detected, even though the incident light is notsufficiently optimized to focus light, but is still better focused thanordinary irradiation. Once the newly developing hologram has beencompleted, the incident phase conjugation wave can focus on this newpoint in the scattering medium. By repeating this process step by step,the focus point can be deepened in the scattering medium.

Another way to deepen the ultrasound focus point may be to begin with alarger ultrasound focus volume, which is large enough to develop thehologram, and gradually reduce the ultrasound focus volume to apredetermined size.

Furthermore, in medical applications, for example to image (monitor) orto treat an abnormal tissue region using this embodiment, the ultrasoundfocus point may be set at the abnormal region by using a prioriinformation provided by other modalities such as X-ray, MRI, ultrasound,or any other diagnostic results.

While the phase conjugation wave is being generated, a monitoring systemto confirm whether the generated phase conjugation wave is focused at aspecific point (e.g., volume 208) inside a scattering medium 209 canoptionally be introduced. One of the monitoring methods is described ina fifth embodiment. In the fifth embodiment, a photoacoustic signal isused for the monitoring. Instead of the photoacoustic signal, afrequency-shifted light signal based on acousto-optic imaging technique,and a cross-sectional reconstructed image with DOT (Diffuse OpticalTomography) technique can be used for the monitoring. In addition, acombination of using the photoacoustic signal and/or thefrequency-shifted light signal and/or the signal for the DOT techniquemight be applicable.

It may be possible to compare the detected signal caused by using thephase conjugation wave or the reconstructed wave, which is designed soas to focus on a specific portion, with a signal caused by using a wave,which is not specifically designed to focus on the specific portion. Tocompare these signals and indicate a result of the comparison to a user,the difference between these signals or the ratio of one signal to theother can be calculated. When the power of the light source and the timeof the irradiation are known, it may be possible for the user toestimate or infer the dose amount of the irradiation from the ratio orthe difference.

First Embodiment

An irradiating apparatus and method according to a first embodiment ofthe present invention will be described below. FIGS. 3A and 3B areschematic diagrams illustrating an exemplary configuration of arecording step (FIG. 3A) and a reproducing step (FIG. 3B), respectively.

The first embodiment includes an acousto-optic imaging technique. Alaser 300 emits an initial light and the initial light is split into anincident light beam 314 and a reference light beam 315 by a beamsplitter 301 in FIG. 3A. The incident light beam 314 and the referencelight beam 315 enter AOM 302 and AOM 305, respectively. The frequenciesof those two AOMs are typically 50 MHz to 80 MHz, and are slightlydifferent by an amount equal to the frequency applied to an ultrasoundsystem 311, which ranges from approximately 1 to tens of megahertz. Therole of these AOMs may be the same as described above.

A lens system 303 controls the beam size of the incident light 314, anda movable mirror 304 controls the incident point on the surface of ascattering medium 312. Once the incident light beam 314 enters thescattering medium 312, the light undergoes multiple scattering processesinside the medium 312.

The ultrasound system 311, which is acoustically matched to the medium312, is operated in advance to form a focus volume 313 which istypically a few mm size at a position in the scattering medium 312. Theultrasound system 311 includes, for example, a linear array probe.Therefore the ultrasound focus volume 313 may be generated at anyposition in the scattering medium 312 by electronic focusing the arrayprobe. Alternatively, the ultrasound focus volume 313 may be provided ata desired position by mechanically scanning the ultrasound transducer,including a circular concave ultrasound transducer or a transducerincluding an acoustic lens. As such a transducer, a transducer using apiezoelectric phenomenon, a transducer using resonance of light, or atransducer using a change in capacity is available.

At least a portion of the incident light beam 314 may reach theultrasound focus volume 313 and interact with ultrasound there. Some ofthe interacted light may reflect back to exit from the scattering medium312 as frequency-shifted light 316. A lens system 310 collects theexiting scattered light onto a dynamic hologram device 307 such as aphotorefractive crystal.

For example, the photorefractive crystal may be Lithium Niobate whichhas a size ranging from several millimeters to a few centimeters and athickness greater than a few hundreds of micrometers to obtainsufficient diffraction efficiency.

The reference light beam 315, which has the same frequency as thefrequency-shifted light 316, illuminates the photorefractive crystal 307via a mirror 306 so that the reference light interferes with thefrequency-shifted light 316. Consequently, the wavefront of thefrequency-shifted light may be recorded as a static refractive indexgrating in the photorefractive crystal 307.

Subsequent illumination of the reference light beam 315 on thephotorefractive crystal 307 after the creation of the hologram acts as aforward pump light. The forward pump light beam 315 is diffracted by theindex grating creating inside the photorefractive crystal 307. Thisdiffracted light and the frequency-shifted light 316 transmitted throughthe photorefractive crystal 307 interfere with each other and can bedetected by a photodetector 309 through a collection lens system 308,for example as disclosed in U.S. Patent Application Publication No.2008/0037367. As for the photodetector 309, a single sensor such as aphotomultiplier tube (PMT) or an avalanche photo diode (APD), can beused. Alternatively, a multi-sensor, such as a CCD or a CMOS, may beused. The photodetector 309 might be used to monitor the holographicmaterial.

As the hologram is being formed, the output from the photodetector 309may increase. After the creation of the hologram, that output signaldoes not increase. Therefore, by monitoring this output signal, it ispossible to confirm the creation of the hologram inside thephotorefractive crystal 307.

Meanwhile, the movable mirror 304 changes its angle so that the incidentlight beam 317 enters the photorefractive crystal 307 substantially inan opposite direction to that of the forward pump light beam 315 in FIG.3B. This incident light beam 317 acts as a backward pump light, andgenerates the phase conjugation (phase conjugate wave) of the inscribedwavefront in the photorefractive crystal 307. This phase conjugationbeam 318 propagates through the lens system 310 to enter the scatteringmedium 312.

Since the phase conjugation beam 318 can retrace its trajectory to theultrasound focus volume 313 in the scattering medium 312, more and morelight can enter this ultrasound focus volume 313 and interact withultrasound. Therefore, much more frequency-shifted light 316 isreemitted from this local volume 313 and is detected through thephotorefractive crystal 307 with lens systems 308, 310 and thephotodetector 309 in FIG. 3B. As a result, the intensity of thefrequency-shifted light which is the signal for acousto-optic imagingcan be enhanced.

During the above whole measurement process, it may be possible that theultrasound system 311 can continue to transmit the ultrasonic wave toform the focus volume 313, and the light beam 315 can continue toilluminate the photorefractive crystal 307, which has been used as areference light, as a forward pump light. At the same time, the backwardpump light beam 317 can illuminate the photorefractive crystal 307 in adirection opposite to the pump light 315 to generate the phaseconjugation beam 318.

In this kind of dynamic holographic method, the hologram which isinscribed in the photorefractive crystal 307 follows the change of itsfrequency-shifted wavefront self-adaptively. This adaptively changedhologram can help the phase conjugation beam 318 generated by thebackward pump light 317 to focus the light in a slightly changedscattering environment in the medium 312. Especially in the case ofbiological tissues, the scattering environment, including the locationof the scatterers, is changing as time advances, due mainly tobiological activities. Since the wavefront of the frequency-shiftedlight at the reproducing step may be different from the wavefront at therecording step, this dynamic hologram method is effective due toself-adaptiveness to generate the phase conjugation in such a medium.

The power of the incident light beam 314 in FIG. 3A or the phaseconjugation light beam 318 can be monitored and adjusted just before itenters the scattering medium (not shown in FIG. 3A and FIG. 3B). Thepower of the laser 300 can be controlled so that the input power islarge enough to obtain the adequate frequency-shifted light in order todevelop the hologram, which can be confirmed by the output signal fromthe photodetector 309, while keeping the power below the maximumexposure for safety when the scattering medium is a biological livingtissue.

In addition, this system may change the intensity of the light betweenthe recording process and the reproducing process. For example, atfirst, a relatively strong light intensity may be injected to obtain thefrequency-shifted light 316 which is sufficient to create the hologram.Next, at the reproducing step, a relatively reduced intensity may beused as the backward pump light beam 317 to generate the phaseconjugation beam 318, in order to save the power consumption whilekeeping sufficient SNR (signal-to-noise) due to the focusing effect.

Furthermore, the ultrasound focus volume 313 inside the scatteringmedium 312 may be scanned and each position of the volume may besequentially subjected to the above process, thus obtaining an opticalproperty distribution such as absorption and scattering in the medium312 as described, for example, in U.S. Pat. No. 6,957,096, which ishereby incorporated by reference in its entirety as though fully andcompletely set forth herein. An image generating unit (not shown) canmap these optical properties in accordance with the positions of therespective focus volume 313 to obtain a three-dimensional spatialdistribution of those optical properties. A photodetector may be used todetect a signal output from the medium in response to an irradiation ofthe reconstructed wave.

Furthermore, the above-described process may be performed using aplurality of desired wavelengths of the laser source 300, and mayoptionally change the photorefractive crystal 307 to obtain functionalinformation, such as a proportion of the constituents of the scatteringmedium 312, e.g., oxy-hemoglobin, deoxy-hemoglobin, water, fat, collagenand an oxygen saturation index of the medium 312, such as when thescattering medium 312 is a biological tissue for medical application.The following are hereby incorporated by reference in their entiretiesas though fully and completely set forth herein: U.S. Pat. No. 6,738,653to Sfez et al, issued May 18, 2004, and U.S. Patent ApplicationPublication No. 2008/0037367 to Gross et al, published Feb. 14, 2008.

A monitoring system to confirm whether the generated phase conjugationwave 318 is focused at a specific point (e.g., the volume 318) inside ascattering medium can optionally be introduced. For example, once thehologram is developed to generate the phase conjugation beam 318, thehologram may be fixed during a following monitoring process. By scanningthe ultrasound focus volume 313 and detecting the acousto-optic signal(frequency-shifted light) through another detector (not shown) such asCCD or CMOS, or PMT (photomultiplier tube), a distribution map of thedetected acousto-optic signal at around and including the focus volume312 can be obtained. This may be used as a monitoring method sinceacousto-optic signal reflects the local optical information where theultrasound 311 is focused. It might be possible to compare the detectedacousto-optic signal caused by using the phase conjugation wave, whichis designed so as to focus on a specific portion, with a signal causedby using a wave, which is not designed to focus on the specific portion.To compare these signals and indicate a result of the comparison to auser, the difference between these signals or the ratio of one signal tothe other can be calculated and the light enhancement irradiation mapcan be obtained. When the power of the light source is known, it mightbe possible for the user to estimate or infer the dose amount of theirradiation from the ratio or the difference.

Any acousto-optic imaging scheme such as parallel detection with CCD maybe applicable for this monitoring.

Second Embodiment

An irradiating apparatus and method according to a second embodiment ofthe present invention will now be described. The configuration of animaging system in this embodiment is same as that of in the firstembodiment shown in FIG. 3A and FIG. 3B, except for addingphotodetectors around the scattering medium 312 (not shown). The imagingsystem in the second embodiment includes a technique called diffuseoptical tomography (DOT).

The flow may also be the same as in the first embodiment until thehologram has been developed in the photorefractive crystal 307. Once thehologram has been created in the photorefractive crystal 307, thebackward pump light beam 317 illuminates the photorefractive crystal 307to generate the phase conjugation beam (including the phase conjugatewave) 318. At this moment, the ultrasound system 311 may be turned offto perform DOT measurement.

After this phase conjugation beam 318 enters the scattering medium 312,it can retrace to the ultrasound focus volume 313 and furthermoreretrace back to the original incident point. The photodetectors placedadequately around the scattering medium 312 can detect the exitingscattered light. It may be possible to restrict or decrease the lightpaths inside the scattering medium 312 by controlling the position ofthe ultrasound focus volume 313 while taking advantage of techniquesused in DOT. Therefore, this imaging system may serve to reduce theill-posedness, which is one of the problems in DOT. As described in theembodiment, when the light is focused on a position in a scatteringmedium, it may become easier to analyze a signal output from the mediumin response to a focused irradiation.

By repeating the above measurement process with different incident lightpoints, the system can collect data to reconstruct the images of theinternal distribution of optical properties such as absorption, and asin DOT. The image forming system (not shown) reconstructs those imagesbased on the measurement data to obtain three-dimensional images ofabsorption and scattering properties distribution inside the medium 312.

It may also be possible that measurement is performed at a plurality ofwavelengths to obtain spectral information, as in the first embodiment,to extract functional information of the biological tissues.

Here, it is possible to perform time-domain measurement by using a pulselaser at an irradiating step and a time-correlated photon countingsystem (not shown), or to perform frequency-domain measurement bymodulating the intensity of the laser 300 output and for example,lock-in detection system (not shown). The following are herebyincorporated by reference in their entireties as though fully andcompletely set forth herein: U.S. Pat. No. 5,441,054 to Tsuchiya, issuedAug. 15, 1995, U.S. Pat. No. 5,477,051 to Tsuchiya, issued Dec. 19,1995, U.S. Pat. No. 5,517,987 to Tsuchiya, issued May 21, 1996, and U.S.Pat. No. 5,424,843 to Tromberg et al, issued Jun. 13, 1995.

A monitoring system to confirm whether the generated phase conjugationwave is focused on a specific point inside a scattering medium canoptionally be introduced. It may be possible to monitor the focusedeffect by monitoring the enhancement distribution map obtained by takingthe ratio of the reconstructed DOT images measured before and after thephase conjugation irradiation. The generated DOT image obtained by usingthe phase conjugation wave, which is designed so as to focus on aspecific portion, can be compared with another DOT image obtained byusing a wave, which is not designed to focus on the specific portion.

It might be possible to compare the detected a signal caused by usingthe phase conjugation wave, which is designed so as to focus on aspecific portion, with a signal caused by using a wave, which is notdesigned to focus on the specific portion. To compare these signals andindicate a result of the comparison to a user, the difference betweenthese signals or the ratio of one signal to the other can be calculated.When the power of the light source is known, it might be possible forthe user to estimate or infer the dose amount of the irradiation fromthe ratio or the difference.

It also may be possible to inject a chemical probe to monitor thefluorescence signal with DOT technique for this monitoring purpose.

Third Embodiment

An irradiating apparatus and method according to a third embodiment ofthe present invention will be described. FIG. 4 is a schematic diagramillustrating an exemplary configuration of an imaging system with theirradiating apparatus according to the embodiment. The system of thisembodiment may include two combined systems, which are an acousto-opticimaging system and a photoacoustic imaging system.

A laser source 400 (a first electromagnetic wave source as a part of afirst irradiating unit) emits initial light and is split into anincident light beam 415 and a reference light beam 416 by a beamsplitter 401. An AOM 402 and AOM 405 have a same role as alreadydescribed above to adjust the frequency. the incident light beam 415enters a scattering medium 409 through an optical system 406.

An ultrasound system 407 including an ultrasound device, which may beacoustically matched to the medium 409, controls an ultrasound focusvolume 408 with size and position inside the scattering medium 409. Atleast a portion of the frequency-shifted light 417 originating from thelocal volume 408 exits from the scattering medium 409 and impinges ontoa photorefractive device 410 to create a hologram by interfering withthe reference light beam 416 reflected from a mirror 403 and 404 (as apart of a second irradiating unit).

During the creation of the hologram inside the photorefractive device410, the acousto-optic signal 418, which is the frequency-shifted light,can be monitored, as necessary, by a photodetector 412 through acollection lens system 411 to confirm the development in the same way asdescribed above in the first embodiment. At this time, thisfrequency-shifted light signal is stored into a memory (not shown) to beused for reconstructing images.

Once the creation of the hologram has been completed, a thirdirradiating unit comprising a pulse laser source 414 (a secondelectromagnetic wave source) for photoacoustic imaging emits a pulselight of several nanoseconds. The pulse light illuminates thephotorefractive device 410 substantially in an opposite direction to thereference light beam 416 to generate the phase conjugation of thefrequency-shifted wavefront inscribed in the photorefractive device 410.The phase conjugation beam (the phase conjugate wave) 419 propagatesbackward to the scattering medium 409.

The ultrasound system 407 can change its operation mode from atransmission mode to a reception mode in order to detect a photoacousticsignal, without changing the focusing setting used for the transmissionmode. Optionally, another ultrasound unit (not shown) can be introducedfor detecting the photoacoustic signal.

Since the incident phase conjugation beam 419 can retrace the trajectoryto the local volume 408 in the scattering medium 409, this incidentlight beam 419 can focus at the local volume 408 that is the measurementvolume for photoacoustic imaging.

The energy of the light absorbed in the local volume 408 locally causesan increase in temperature, thus resulting in expansion of the volume ofthis local region and an acoustic wave (photoacoustic signal) isgenerated. According to the equation (1), the photoacoustic signal P isproportional to the local absorption coefficient μ_(a) and light fluencerate Φ at that point.

P=Γμ _(a)Φ  (1)

where Γ is Grueneisen coefficient (heat-acoustic conversion efficiency).

Therefore, a higher fluence rate generates a larger photoacousticsignal. Since the incident phase conjugation beam 419 can focus light atthe local volume 408, a larger photoacoustic signal is generated fromthis local volume 408. The ultrasound system 407 which is set to focusthat volume 408 in the reception mode detects the photoacoustic signaloriginated from that volume 408. Alternatively or additionally, anotherultrasound detector may be provided to detect a signal output from themedium 409 in response to an irradiation by the reconstructed wave 419.

FIG. 5 shows an exemplary operation flow of this system. At first, theparameter conditions regarding the focus of the ultrasound system 407,such as the size or the position of the focus volume, is set at S500,and then the ultrasound system 407 transmits pulsed ultrasonic waves toform the ultrasound focus volume 408. At S501, the laser 400 radiatesthe initial light beam.

Through the acousto-optic imaging, the acousto-optical signal(frequency-shifted light) is monitored by the photodetector 412 at S502,and the photodetector 412 confirms whether or not the creation of thehologram is completed at S503. These processes at S502 and S503 may berepeated until the creation of the hologram is confirmed. In addition,before moving to S504 after completing the hologram, the acousto-opticalsignal can be stored.

Once the hologram has been developed, then the laser 400 is turned offand the operation mode for the ultrasound system 407 is changed from atransmission mode to a reception mode at S504. After that, the laser 414radiates a pulsed light beam to the photorefractive device 410 at S505in substantially an opposite direction to the reference light beam 416to generate the phase conjugation light beam 419. At S506, thephotoacoustic signal is detected by the ultrasound system 407.

This is an exemplary basic operation flow, and if the measurementposition for photoacoustic imaging needs to be changed, the ultrasoundsystem may change its focus position and go back to S500 and repeat theentire flow (S500 to S506).

An image generating process may follow the measurement. An imagegenerating unit (not shown) may reconstruct three-dimensional images byusing the above data. The image generating unit maps an absorptionsignal obtained by photoacoustic measurement in accordance with thepositions of the ultrasound focus volume 408. At this time, anacousto-optic signal stored at S503 is read and used to generate ascattering distribution image in the same way. Since photoacoustic imageis sensitive to absorption, while acousto-optic image is sensitive toscattering, by combining both measurement results, absorption andscattering distribution images can be generated.

Furthermore, it is possible to add one more steps before S500. That is,a pulsed ultrasonic wave may be transmitted from the ultrasound system407 and an ultrasonic echo, serving as a reflected wave, may be receivedby the ultrasound system 407. This ultrasound echo measurement may beperformed while the direction in which the pulse ultrasonic wave istransmitted is changed relative to the scattering medium 409, thusobtaining structural data regarding the inside of the scattering medium409. The ultrasound focus volume 408 can be set by taking advantage ofthe structural data obtained by the ultrasound echo measurement, forexample, by setting at a position where a characteristic difference canbe seen in the echo image.

Alternatively, it may possible to select the measurement point ofphotoacoustic imaging by analyzing an acousto-optic signal obtained andstored at S503. At first, an acousto-optic imaging system may be used tofind an area to be measured by the photoacoustic system. If distinctivechanges are found in the acousto-optic signal, then the laser 414 forphotoacoustic imaging emits pulse light. Or it may be also possible touse the photoacoustic imaging system to search the characteristic regioninstead of using the acousto-optic imaging system before deciding theultrasound focus volume 408.

The imaging system of this embodiment can also be achieved with theconfiguration shown in FIGS. 3A and 3B. In this case a light source unit300 may emit light from at least two different lasers. One may be alaser for an acousto-optic system and the other may be a pulse laser fora photoacoustic system. The lasers can be switched from one to the otherbetween the recording step and the reproducing step.

By focusing light at the measurement volume of photoacoustic imaging, itmay be possible to enhance the measurement depth and SNR ofphotoacoustic imaging. The following are hereby incorporated byreference in their entireties as though fully and completely set forthherein: U.S. Pat. No. 4,385,634 to Bowen, issued May 31, 1983, U.S. Pat.No. 5,840,023 to Oraevsky et al, issued Nov. 24, 1998, and U.S. Pat. No.5,713,356 to Kruger, issued Feb. 3, 1998. An imaging system includingtwo combined systems which are an acousto-optic imaging system and aphotoacoustic imaging system may be realized to obtain a clearer imageor a useful image for diagnosis.

A monitoring system to confirm whether the generated phase conjugationwave is focused at a specific point inside a scattering medium canoptionally be introduced. It might be possible to compare a detected asignal caused by using the phase conjugation wave or reconstructed wave,which is designed so as to focus on a specific portion, with a signalcaused by using a wave, which is not designed to focus on the specificportion. To compare these signals and indicate a result of thecomparison to a user, the difference between these signals or the ratioof one signal to the other can be calculated. When the power of thelight source is known, it might be possible for the user to estimate orinfer the dose amount of the irradiation from the ratio or thedifference. One of the monitoring methods is described in a fifthembodiment.

Fourth Embodiment

An irradiating apparatus and method according to a fourth embodiment ofthe present invention will be described. FIG. 6 is a schematic diagramillustrating an exemplary configuration of a light irradiating apparatusto deliver light into a specific position in a disordered scatteringmaterial.

An irradiator comprising a laser source 600 emits an initial light beamwhich is split into an incident light beam 616 and a reference lightbeam 617 by a beam splitter 601. A lens system 606 expands the incidentlight beam 616 to irradiate the material 607. AOMs 603 and 604, andmirrors 602 and 613 may be placed on the path of the reference lightbeam 617 so that the frequency of the reference light can be adjustable.

A modulator comprising an ultrasound system 609 may be acousticallymatched to the material 609 and irradiate the ultrasonic wave. Anultrasound focus volume 608 is formed in the material 607 by theultrasound system 609.

As already described above, some of the frequency-shifted light 619originating from the focus volume 608 exits from the surface of thematerial 607 and is guided to a detector comprising a CCD sensor 612through a lens system 610 and a dichroic mirror 611. Here, a CMOS sensoror area sensors with an image intensifier, or EMCCD (ElectronMultiplying CCD) are also applicable. The reference light beam 617 isreflected by a mirror 605 to reach the CCD 612 eventually to create ahologram, which is based on an interference between the reference lightbeam 617 and the frequency-shifted light 619 on the CCD 612.

A processing unit (not shown) is provided in this system. Thisprocessing unit controls a generator comprising a spatial lightmodulator (SLM) 614, such as a liquid crystal on silicon (LCOS), inorder to generate a reconstructed light which may be equivalent to thephase conjugation (phase conjugate wave) by utilizing a digitalholography technique.

The interferogram of the frequency-shifted light can be obtained by aphase-shifting digital holography technique. At the CCD 612 plane,non-frequency-shifted light, frequency-shifted light and the referencelight are impinging. The frequency of the reference light (f_(R)) can beadjusted, for example according to the following equation, by adjustingthe AOM 603 and 604.

f _(R) =f _(U) +f _(A) +f _(C) /N  (2)

where, f_(U) is the frequency of unshifted light, f_(A) is the frequencyof the ultrasound, f_(C) is the frame rate of the CCD 612 and N is thenumber of measurements for phase shifting method. Since the CCD 612 actsas a low-pass filter, mainly the component of the interferogram betweenthe frequency-shifted light 619 and reference light beam 617 carries thefringes, which varies slowly in time so that the CCD 612 can efficientlydetect the interferogram (the digital hologram).

The phase distribution is obtained by calculating the phase of thedetected frequency-shifted light on each pixel from the digital hologramwith a phase-shifting method. The processing unit sets the phase valueof each pixel in the SLM 614 according to the phase distributionobtained by the digital hologram. At this time, the difference of theoptical length between the CCD 612 and the SLM 614 or any other systemerror may be calibrated, and the phase values may be corrected.Alternatively, the CCD 612 and the SLM 614 may be arranged so that theoptical length from the exit plane of the material 607 to those devicesis the same.

The SLM 614 modulates the phase of light emitted by a laser 615. Thisphase modulation develops a reconstructed light beam 618 which may beequivalent to the phase conjugation and can retrace the trajectory backto the ultrasound focus volume 608 in the material 607. Thereconstructed light beam 618 developed by the SLM 614 is configured toirradiate the material 607. In case the apparatus may be used forcreating an image inside the material, a signal output from the materialthat results from the irradiation of the material by the reconstructedlight beam 618 can be detected to form the image, as already describedin the other embodiment.

If the CCD 612 has a larger number of pixels compared to the SLM 614,the CCD 612 may perform binning so that the number of pixels betweenthem is equal and those pixels are corresponding with each other.

Furthermore, any other digital technique used in the digital holographymay be applied to improve the characteristic of the reconstructed light.

The irradiating apparatus described in the fourth embodiment can also beapplicable to therapy or treatment such as photodynamic therapy inbiological tissues. The configuration of the system in a fifthembodiment may be same as that shown in FIG. 6.

Once the digital hologram has been obtained and the SLM 614 is ready forthe phase modulation in accordance with the digital hologram, the laser615 can shoot light which has a relatively stronger power compared tothe light emitted by the laser 600 used to create the digital hologram.The light power of the laser 615 can be controlled depending on thetreatment.

Furthermore, many kinds of lasers can be applicable depending on thepurpose of the therapy or treatment (e.g., femto second pulse to pico,nano, micro etc.). The digital hologram can be applied to the system ofany one or more of the first to third embodiments.

The reconstructed light beam 618 for therapy whose phase can becontrolled by the SLM 614 can reach the ultrasound focus volume 608 todeliver light energy at that tissue region where the treatment isneeded. The position of the ultrasound focus volume 608 may be set byreferring to other diagnostic results.

By using the embodiment according to the present invention, it may bepossible to deliver the high energy density of light efficiently to aspecific point with less damage.

A monitoring system to confirm whether the generated reconstructed lightbeam is focused at a specific point inside a scattering medium can beintroduced as necessary. One of the monitoring methods is described in afifth embodiment.

Fifth Embodiment

In order to confirm whether light is focused at a specific point insidea scattering medium in practical situation, the monitoring method can beadded to any one or more of the above described embodiments.

To monitor the light intensity distribution around the focus spot area(not just only at the focus spot), the area to be monitored can be setby a user.

Since the focus spot size or area can be determined by an ultrasoundsystem setting (those are determined by ultrasound focus size), onemight predict that the expected focus spot size would be the same as theultrasound focus size. However, it may actually deviate from theprediction due to the turbulence of the ultrasound inside the mediumattributed to the fact that the speed of the ultrasound will change.Therefore, it may be advantageous and even necessary to monitor thelight intensity distribution at the predicted focus spot area, and alsoaround the area. A feedback system can be used for tuning the ultrasoundsystem based on monitoring in order to move or shape the light focusingspot for practical situations.

FIG. 7 illustrates a schematic diagram of an exemplary configurationwhich has an irradiating apparatus with a monitoring system. A laser 700can emit an initial light, and the initial light is split into anincident light 717 and a reference light 718 by a beam splitter 701.

The reference light 718 passes through two external modulators, such asacousto-optic modulators (AOMs) 703 and 704, which can be drivenindependently by clocks of frequencies which are adjusted such that thefrequency differences between them is approximately equal to thefrequency applied to an ultrasound system 709. A beam splitter 702 canbe used in the optical system.

For example, if the frequency of the AOM 703 is 72 MHz and the frequencyof the AOM 704 is −70 MHz, then the frequency of the ultrasound system709 is 2 MHz. Instead of using the two AOMs 703 and 704 in the path ofthe reference light 718, the AOM 703 (or 704) can be placed in the pathof the incident light 717 and the AOM 704 (or 703) can be placed in thepath of the reference light 718. When one AOM can modulate the light bya required frequency, there may be no need to use the two AOMs.

A lens system 706 can control the beam size of the incident light 717 onthe surface of a scattering medium 707 where the light undergoesmultiple scattering processes inside the medium 707. The ultrasoundsystem 709, which is acoustically matched to the medium 707, is operatedin advance to form a focus volume 708 which may vary from several tensof microns to a few mm size at a position in the scattering medium 707.The ultrasound system 709 can include, for example, a linear arrayprobe. Therefore, the ultrasound focus volume 708 may be provided at adesired position by electronic focusing the array probe. Alternatively,the ultrasound focus volume 708 may be provided at a desired position bymechanically scanning the ultrasound transducer or a transducerincluding a circular concave ultrasound transducer or a transducerincluding an acoustic lens. Transducers such as a transducer using apiezoelectric phenomenon, a transducer using resonance of light, and atransducer using a change in capacity may be available.

At least a portion of the incident light 717 may reach the ultrasoundfocus volume 708 and interact with ultrasound there. Some of theinteracted light whose frequency is shifted by the frequency applied tothe ultrasound system 709 may transmit to exit the medium 707 as asignal light 719.

A lens system 710 can collect the signal light 719 onto a detectorcomprising a CCD sensor 712. Here a CMOS sensor or area sensors with animage intensifier, or EMCCD (Electron Multiplying CCD) are alsoapplicable as the detector 712.

The reference light 718, which has the same frequency as thefrequency-shifted signal light 719, illuminates the CCD 712 via mirrors705 and 711 so that the reference light interferes with the signal light719 to create a hologram on the CCD 712.

A processing unit (not shown) is provided in this system. Thisprocessing unit can be configured to control a generator comprising aspatial light modulator (SLM) 715, such as a liquid crystal on silicon(LCOS), in order to generate a reconstructed light which may beequivalent to the phase conjugation (phase conjugation wave) byutilizing digital holographic technique.

The phase information of the interferogram of the frequency-shiftedlight can be retrieved by a phase-shifting digital holography technique.At the CCD 712 plane, non-frequency-shifted light, frequency-shiftedlight and the reference light 718 are impinging. The frequency of thereference light (f_(R)) is adjusted, for example according to thefollowing equation, by adjusting the AOM 703 and 704.

f _(R) =f _(U) +f _(A) +f _(C) /N  (3)

where, f_(U) is the frequency of non-shifted light, f_(A) is thefrequency of the ultrasound, f_(C) is the frame rate of the CCD 712 andN is the number of measurements for phase shifting method.

Since the CCD 712 can act as a low-pass filter, mainly the component ofthe interferogram between the signal light 719 and reference light 718carries the fringes, which varies slowly in time so that the CCD 712 canefficiently detect the interferogram (the digital hologram).

The phase distribution of the measured wavefront is obtained bycalculating the phase of the detected frequency-shifted light on eachpixel from the digital hologram with a phase-shifting method. Theprocessing unit sets the digitally reversed measured phase value(wavefront) of each pixel in the SLM 715 according to the phasedistribution obtained by the digital hologram. For example, if themeasured phase is φ(x,y) on the CCD x-y plane, the reversed phase−φ(x,y) is set on the SLM 715.

At this time, a beam splitter 721 may be placed such that the opticallength from the exit plane of the medium 707 to the CCD 712 and the SLM715 are the same (symmetric). Therefore, every pixel of the CCD 712 toform an image matches with a corresponding pixel of the SLM 715 (the CCD712 and the SLM 715 can be aligned pixel by pixel). Alternatively, theCCD 712 may be placed at the symmetric position as what CCD 712 ideallymay be placed by using a lens system to adjust the pixel size betweenthe CCD 712 and the SLM 715.

It also may be possible to record the wavefront of the frequency-shiftedlight by off-axis digital holography technique and extract the phaseinformation. The off-axis digital holography technique can be explainedas follows. The signal light 719 and the reference light 718 canpropagate in different direction to record the hologram in the off-axisconfiguration. The off-axis configuration allows an angle (e.g.,approximately one degree or so) between the signal light 719 and thereference light 718 as described in FIG. 7. To acquire information aboutthe wavefront of the signal light 719, which is frequency-shifted by theultrasound, data obtained from the detector 712 corresponding to theinterferogram (hologram) can be Fourier transformed, and then spatiallyhigh-pass filtered to be isolated as a cross-correlation term betweenthe signal light and reference light. This process can eliminate thebackground components from the Fourier transformed data. Then thecross-correlation term is Fourier transformed to retrieve the phaseinformation of the signal light 719. Here, it may optionally use Hilberttransform instead of using Fourier transform, to obtain the phaseinformation. As to the off-axis configuration, U.S. Pat. Nos. 6,078,392issued on Jun. 20, 2000 to Thomas, and 6,262,818 issued on Jul. 17, 2001to Cuche are hereby incorporated by reference in their entirety asthough fully and completely set forth herein. When the off-axisconfiguration is used, the frequency of the reference light 718 can beadjusted to be a value which is similar to the frequency of the signallight 719 (i.e., the frequency-shifted light), instead of adjustingbased on the equation (3).

A laser 713 whose wavelength may be same as that of the laser 700 emitsa pulse light 720 of several nanoseconds for providing a reconstructedlight 738. A lens unit 714 can be used as necessary. The SLM 715 canmodulate the phase of the pulse light 720 such that a reconstructedlight 738 may be equivalent to the phase conjugation and can retrace thetrajectory back to the ultrasound focus volume 708 in the medium 707.The reconstructed light 738 developed by the SLM 715 is configured toirradiate the medium 707 via mirror 721. The width of the pulse light720 may be selected, for example, from a range between severalnanoseconds and several hundreds of nanoseconds.

The reconstructed light 738 can retrace to the local volume 708 in thescattering medium 707. The energy of the light absorbed in the localvolume 708 locally causes an increase in temperature, thus resulting inexpansion of the volume of this local region, and an acoustic wave(photoacoustic signal) is generated.

According to the equation (4), the photoacoustic signal P isproportional to the local absorption coefficient μ_(a) and light fluenceΦ at that point 708 in the medium 707.

P({right arrow over (r)})=Γ({right arrow over (r)})μ_(a)({right arrowover (r)})Φ({right arrow over (r)})  (4)

where Γ is Grueneisen coefficient (heat-acoustic conversion efficiency),and {right arrow over (r)} is the position in the scattering medium,respectively.

Therefore, the higher the fluence the larger the photoacoustic signal.Since the reconstructed light 738 can focus light at the local volume708, a larger photoacoustic signal may be generated at this local volume708.

A second ultrasound system 716 can act as a detecting unit and/ordetector to measure the photoacoustic signal generated by thereconstructed light 738 around the local volume 708 to monitor thefocused light distribution in the medium 707 around the area in responseto the irradiation by the reconstructed light 738. Instead of using thesecond ultrasound system 716, the ultrasound system 709 can be used fordetecting the photoacoustic signal. The second ultrasound system 716 (orthe ultrasound system 709) can be set to monitor the light distributionaround the local volume 708 in addition to the local volume 708. Theregion to be monitored by the ultrasound system 716 (or 709) can belarger than the local volume 708.

An image generating process may follow the photoacoustic measurement. Animage generating unit (not shown) may reconstruct three-dimensionalimages by using the above obtained photoacoustic signal. The imagegenerating unit maps the three-dimensional distribution of photoacousticsignal P(F) across the measurement volume including the local volume708.

Here explanation regarding a monitoring system is made by using aphotoacoustic signal. A transducer (ultrasound detector) to detect thesignal may be placed so as to surround the medium 707.

Since the photoacoustic signal depends on Grueneisen coefficientΓ({right arrow over (r)}) and absorption coefficient μ_(a)({right arrowover (r)}) which may vary position to position in addition to the lightfluence Φ({right arrow over (r)}) at a position, a reconstructedthree-dimensional distribution of photoacoustic signal might notdirectly reflect the distribution of the light fluence.

Therefore, in order to compare the light distribution from position toposition, a ratio of at least two photoacoustic signal distributions canbe calculated. The distributions can correspond to the photoacousticsignal obtained by using normal irradiation and focused irradiation(reconstructed light 738). The photoacoustic signal obtained by usingnormal irradiation can be used as a background signal.

The Grueneisen coefficient Γ({right arrow over (r)}) and absorptioncoefficient μ_(a)({right arrow over (r)}) are assumed to be constantwith time, though they are position dependent. By taking the ratio,obtained distribution can reflect the light fluence enhancementdistribution.

$\begin{matrix}{\frac{P_{1}\left( \overset{\rightarrow}{r} \right)}{P_{0}\left( \overset{\rightarrow}{r} \right)} = \frac{\Phi_{1}\left( \overset{\rightarrow}{r} \right)}{\Phi_{0}\left( \overset{\rightarrow}{r} \right)}} & (5)\end{matrix}$

where P₀({right arrow over (r)}) is the background photoacoustic signalwith fluence Φ₀({right arrow over (r)})obtained by normal irradiationand P₁({right arrow over (r)}) is the photoacoustic signal with fluenceΦ₁({right arrow over (r)}) obtained by focused irradiation.

The normal irradiation for obtaining the background signal may beperformed by emitting a pulse light from the laser 713 and the SLM 715,which is configured not to modulate the phase of the pulse light andconfigured to just act as a mirror to irradiate the medium 707.

The ultrasound system 716 can measure the photoacoustic signal at aroundan area including the local volume 708 to obtain the backgroundphotoacoustic signal distribution P_(0({right arrow over (r)}).)

The operation flow is explained below in accordance with FIG. 8. At stepS800, several parameters regarding the focus properties such as spotsize or focus position are set and the ultrasound system 716 isconfigured to measure the photoacoustic signal at around the definedarea.

At step S801, a first irradiating unit, i.e. the laser 713 emits a pulselight (or a series of pulses) to measure the photoacoustic signalP₀({right arrow over (r)}) at around the defined area including theexpected focus spot, while the SLM 715 is working as a mirror. Thismeasured photoacoustic signal is considered as a backgroundphotoacoustic signal.

Then at step S802, the laser 713 stops emitting the light pulses and thelaser 700 emits light (CW or pulse light), and at the same time theultrasound system 709 shoots ultrasound pulses which satisfy theconditions set at step S800, such as spot size or position, to generatethe frequency-shifted light (signal light 719).

At step S803, the interferogram (the digital hologram) may be detectedby the CCD 712. Furthermore, by the phase-shift method, the wavefront(the phase information) of the signal light 719 may be retrieved. Themeasured wavefront is digitally reversed and is sent to the SLM 715, andthe phase values are set to modulate the incoming light at step S804.

In the next step S805, the pulse light (or a series of pulses) isemitted from a second irradiating unit, i.e. the laser 713, to measurethe photoacoustic signal P₁({right arrow over (r)}) around the area.After the laser 700 has been turned off or prevented from irradiatingthe medium 707, the pulse light can be emitted from the laser 713.

Three dimensional light distribution map based on the eq. (5) isgenerated at step S806 to monitor the distribution to see whether thefocus effect satisfies the condition at step S807 (e.g., a monitoringunit monitors whether the particular portion is irradiated by thereconstructed wave). If it does not, the ultrasound focusing parameters,such as amplitude or timing of ultrasound shooting from each transducerof the array probe for beam forming, can be tuned at step S808 and thenthe process goes back to step S802 (or S801) to update the lightdistribution around the area until the focusing condition is satisfied.Instead of tuning the ultrasound focusing parameters at step S808 or inaddition to tuning the ultrasound focusing parameters, it can bepossible to change the phases of any one or more of the pixels on theSLM 715 directly to tune the focusing properties.

This monitoring process may be repeated during the light delivery to thefocus spot 708. The laser 713 can comprise two different laser sourceswith a same wavelength. One may be for photoacoustic measurement tomonitor light distribution inside the medium 707 and the other one(i.e., third light source) may be for an application purpose, which maybe imaging or therapy, and depending on the purpose, the third lightsource may be CW laser or pulse laser. After the step S807, the otherlight source (third light source) which can be used for light focusing(the previous pulse light is just for monitoring purpose) may emit thelight.

The emitted light from the third light source may also retrace and focuslight at the point 708. During this irradiation, the above monitoringprocess may be performed. For example, emitting light from the thirdlight source and the monitoring process (S802 to S808) may be performedalternately. Or simultaneous emission from both light sources may bepossible.

Furthermore, in FIG. 7 the second ultrasound system can be used todetect the photoacoustic signal for monitoring purposes. It may bepossible to detect the photoacoustic signal by using just one ultrasoundsystem which is same as the system 709 used for generatingfrequency-shifted light, by changing the mode from transmission toreception mode, thereby allowing for removal of the second ultrasoundsystem 716.

Moreover, if it is necessary to consider the time-dependence of theGrueneisen coefficient or absorption coefficient, the step S801 forbackground photoacoustic measurement may be included in the steps totune the focus condition. Therefore, after the step S808, the processmay go back to S801. The approach can also be applied to a system withhologram material such as photorefractive material, instead of thedigital hologram.

The above monitored images may be overlaid with other images such as MRIimage, X-ray image, or ultrasound imaging, such as for example in a casewhere the point where light focusing is desired can be determined fromthose other images. In such a case, the photoacoustic images (monitoringimages) may be co-registered with those images by being overlaid withthe images. The focusing parameters may be set based on the informationobtained by those other images at S800. The monitoring images areoverlaid with those images to confirm whether the light is focused atthe point with desired spot size or enhancement.

As described above, the fifth embodiment can provide a method forirradiating a medium. The method can comprise the following steps:

(1) Irradiating the medium with an electromagnetic wave which isscattered in the medium, and is not designed to focus on the particularportion in the medium;(2) Detecting a first signal caused by irradiating the medium with theelectromagnetic wave;(3) Irradiating the medium with a reconstructed wave which is designedto focus on the particular portion in the medium;(4) Detecting a second signal caused by irradiating the medium with thereconstructed wave;(5) Monitoring, based on the first and second signals, that theparticular portion is irradiated by the reconstructed wave.

The first signal obtained in the step (2) includes a signal from theparticular portion and a first area around the particular portion. Thesecond signal in the step (4) can include a signal from the particularportion. And the second signal might be set to include a signal from theparticular portion and a second area around the particular portion. Thefirst or second area in the medium can be set by a user. The first areacan be the same as the second area.

The first and second signals can be detected repeatedly whilemonitoring. Either or both of the electromagnetic wave for the firstirradiating in step the (1) and the reconstructed wave for the secondirradiating in the step (3) can include a pulse wave to cause aphotoacoustic signal in the medium.

The reconstructed wave in the step (3) can be irradiated to theparticular portion in the medium by recording and reconstructingprocesses. The recording process comprises: irradiating the medium withan electromagnetic wave which is scattered in the medium and modulatedin frequency at the particular portion in the medium; and acquiringinformation corresponding to an interference pattern formed byinterference of the modulated electromagnetic wave with a referencewave. And the reconstructing process can comprise generating thereconstructed wave based on the obtained information about theinterference pattern.

This fifth embodiment can enable users to confirm the light focus spotdistribution and adjust the position or shape of the spot or enhancementfactor by monitoring the distribution of the light intensity.Furthermore, if this embodiment is combined with other imaging systemsand/or the images are overlaid with other images, one can confirm thefocusing properties by comparing the information obtained from the otherimages, such as detail structures obtained with the other imagingsystems, so that one may be able to target a specific point and tune itduring the focusing operation.

The above described monitoring system can also be incorporated into anyone or more of the first to fifth embodiments. Also, in addition to ofthe photoacoustic signal, frequency-shifted light based on acousto-opticimaging technique, and a cross-sectional reconstructed image with DOTtechnique, can be used either alone or in combination for themonitoring.

In the monitoring process, it may be possible to compare a detected asignal caused by using the phase conjugation wave or reconstructed wave,which is designed so as to focus on a specific portion, with a signalcaused by using a wave, which is not designed to focus on the specificportion. To compare these signals and indicate a result of thecomparison to a user, the difference between these signals or the ratioof one signal to the other can be calculated. When the power of thelight source is known, it may be possible for the user to estimate orinfer the dose amount of the irradiation from the ratio or thedifference.

The described embodiments can also be applied to fluorescence imagingwhich uses a chemical probe (molecules) to obtain biochemicalinformation such as abnormality of the tissue, for example, by settingthe ultrasound focus volume to the point where the fluorescence probe islocated. The reproducing step for irradiation thereof may be the same asalready described above. If the location of the chemical probe is notcertain, then the ultrasound focus volume can simply be scanned toirradiate inside the scattering medium one position at a time. Byfocusing light at the position where the fluorescence probe is located,it may be possible to obtain high contrast images of the target, such asfor example a tumor.

As has already been described, the embodiments according to the presentinvention can be applicable to a variety of optical imaging or therapyor apparatuses for the purpose of concentrating light at specificpoints, which may be controllable, inside the scattering medium.

While the embodiments according to the present invention have beendescribed with reference to exemplary embodiments, it is to beunderstood that the present invention is not limited to the abovedescribed embodiments. The scope of the following claims is to beaccorded the broadest interpretation so as to encompass all suchmodifications and equivalent structures and functions.

1. A method for irradiating a medium with a wave which is designed tofocus on a particular portion in the medium is provided, the methodcomprising: irradiating the medium with an electromagnetic wave which isscattered in the medium, and is not designed to focus on the particularportion in the medium; detecting a first signal caused by irradiatingthe medium with the electromagnetic wave; irradiating the medium with areconstructed wave which is designed to focus on the particular portionin the medium; detecting a second signal caused by irradiating themedium with the reconstructed wave; and monitoring, based on the firstand second signals, that the particular portion is irradiated by thereconstructed wave.
 2. The method for irradiating the medium accordingto claim 1, wherein the first signal includes a signal from theparticular portion and a first area around the particular portion. 3.The method for irradiating the medium according to claim 2, wherein thesecond signal includes a signal from the particular portion and a secondarea around the particular portion.
 4. The method for irradiating themedium according to claim 3, wherein the first area is the same as thesecond area.
 5. The method for irradiating the medium according to claim2, further comprising setting the first area in the medium to bedetected with the first signal.
 6. The method for irradiating the mediumaccording to claim 1, wherein detecting of the first and second signalsis executed repeatedly while monitoring.
 7. The method for irradiatingthe medium according to claim 1, wherein the electromagnetic wave forthe irradiating is a pulse wave to cause a photoacoustic signal in themedium.
 8. The method for irradiating the medium according to claim 1,wherein the electromagnetic wave comprises a pulse wave to cause a firstphotoacoustic signal, and the reconstructed wave for the secondirradiating comprises a pulse wave to cause a second photoacousticsignal in the medium, and a ratio of the second photoacoustic signal tothe first photoacoustic signal is calculated while monitoring.
 9. Themethod for irradiating the medium according to claim 1, wherein theelectromagnetic wave for the irradiating is a wave to cause anacousto-optic signal in the medium.
 10. The method for irradiating themedium according to claim 1, wherein the electromagnetic wave for theirradiating is a wave to cause a diffuse optical signal in the medium.11. The method for irradiating the medium according to claim 1, whereinmonitoring includes comparing the second signal with the first signal.12. The method for irradiating the medium according to claim 1, whereinthe reconstructed wave is formed by a process, the process comprising:irradiating the medium with an electromagnetic wave which is scatteredin the medium and modulated in frequency at the particular portion inthe medium; acquiring information related to an interference patternformed by interference of the modulated electromagnetic wave with areference wave; and generating the reconstructed wave based on theacquired information.
 13. The method for irradiating the mediumaccording to claim 1, wherein the reconstructed wave is a phaseconjugation wave.
 14. An apparatus for irradiating a medium with a wavewhich is designed to focus on a particular portion in the medium, theapparatus comprising: a first irradiating unit configured to irradiatethe medium with an electromagnetic wave which is scattered in themedium, and is not designed to focus on the particular portion in themedium; a second irradiating unit configured to irradiate the mediumwith a reconstructed wave which is designed to focus on the particularportion in the medium; a detecting unit configured to detect a firstsignal caused by the first irradiating unit and a second signal causedby the second irradiating unit; and a monitoring unit configured tomonitor, based on the first and second signals, that the particularportion is irradiated by the reconstructed wave.
 15. An apparatuscomprising: a light source configured to irradiate a medium with anelectromagnetic wave, and to be used for a reference wave; a modulatorconfigured to modulate a frequency of the electromagnetic wave at aparticular portion in the medium; a first detector configured to obtaininformation related to an interference pattern formed by interference ofthe modulated electromagnetic wave with the reference wave; a generatorconfigured to generate an electromagnetic wave light beam which isscattered in the medium, and is not designed to focus on the particularportion in the medium, and configured to generate a reconstructed wavewhich is designed, based on the obtained information, so as to focus onthe particular portion in the medium; and a second detector configuredto detect a first signal from the medium, caused by the electromagneticwave, and configured to detect a second signal from the medium, causedby the reconstructed wave.
 16. The apparatus according to claim 15,wherein the modulator comprises an ultrasound device.
 17. The apparatusaccording to claim 15, wherein the generator comprises a light sourceand a spatial light modulator to form the reconstructive wave.
 18. Anapparatus comprising: a light source configured to irradiate a mediumwith an electromagnetic wave, a frequency of which is modulated at aparticular portion in the medium, and configured to be used for areference wave; a holographic material configured to acquire informationrelated to an interference pattern formed by interference of themodulated electromagnetic wave with the reference wave, and forgenerating a reconstructed wave which is designed, based on the acquiredinformation, so as to focus on the particular portion in the medium; anda detector configured to detect a first signal from the medium when awave, which is scattered in the medium and is not designed to focus onthe particular portion in the medium, is irradiated to the medium, andconfigured to detect a second signal from the medium, caused by thereconstructed wave.
 19. An apparatus comprising: a light sourceconfigured to irradiate a medium with an electromagnetic wave, afrequency of which is modulated at a particular portion in the medium,and configured to be used for a reference wave; a holographic materialholding unit configured to hold a holographic material for acquiringinformation related to an interference pattern formed by interference ofthe modulated electromagnetic wave with the reference wave, and forgenerating a reconstructed wave which is designed, based on the acquiredinformation, so as to focus on the particular portion in the medium; anda detector configured to detect a first signal from the medium when awave, which is scattered in the medium and is not designed to focus onthe particular portion in the medium, is irradiated to the medium, andconfigured to detect a second signal from the medium, caused by thereconstructed wave.
 20. The method for irradiating the medium accordingto claim 19, wherein the reconstructed wave is a phase conjugation wave.